Morphological changes, nitric oxide production, and phagocytosis are triggered in vitro in microglia by bloodstream forms of Trypanosoma brucei
Morphological changes, nitric oxide production, and phagocytosis are triggered in vitro in microglia by bloodstream forms of Trypanosoma brucei
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DOI：
10.1038/s41598-018-33395-x
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发表时间：
2018-10-09
影响因子：
4.6
通讯作者：
Duszenko, Michael
中科院分区：
文献类型：
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作者：
Figarella, Katherine;Uzcategui, Nestor L.;Duszenko, Michael
鞭毛寄生虫布鲁氏锥虫是非洲人类锥虫病（HAT）的病原体。锥虫通过一种尚不清楚的机制进入中枢神经系统（CNS），侵入脑实质，如果不加以治疗，可引起致命的脑病。锥虫是一种快速分裂的生物，没有任何免疫反应，可以在短时间内杀死宿主。然而，感染的个体分别存活6-12个月或3年以上的急性和慢性形式。因此，只有当大脑防御系统崩溃时，才会发生致命的脑病。在这里，我们评估了锥虫和小胶质细胞之间的相互作用，小胶质细胞是中枢神经系统内的主要免疫效应细胞。通过原代小胶质细胞和寄生虫的共培养，我们发现了小胶质细胞吞噬锥虫的明确证据。小胶质细胞的激活也很明显；其超微结构分析显示，在感染或退行性疾病引起氧化应激的活化小胶质细胞中发生了变化。因此，在小胶质细胞/寄生虫共培养的上清液中检测到一氧化氮产量的增加。总之，我们的结果表明，小胶质细胞对寄生虫的存在作出反应，导致寄生虫的吞噬和消除。
The flagellated parasite Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (HAT). By a mechanism not well understood yet, trypanosomes enter the central nervous system (CNS), invade the brain parenchyma, and cause a fatal encephalopathy if is not treated. Trypanosomes are fast dividing organisms that, without any immune response, would kill the host in a short time. However, infected individuals survive either 6-12 months or more than 3 years for the acute and chronic forms, respectively. Thus, only when the brain defense collapses a lethal encephalopathy will occur. Here, we evaluated interactions between trypanosomes and microglial cells, which are the primary immune effector cells within the CNS. Using co-cultures of primary microglia and parasites, we found clear evidences of trypanosome phagocytosis by microglial cells. Microglia activation was also evident; analysis of its ultrastructure showed changes that have been reported in activated microglia undergoing oxidative stress caused by infections or degenerative diseases. Accordingly, an increase of the nitric oxide production was detected in supernatants of microglia/parasite co-cultures. Altogether, our results demonstrate that microglial cells respond to the presence of the parasite, leading to parasite's engulfment and elimination.